Drs. Shasha and Harrison provide an excellent review of
the problem of anemia in patients receiving definitive radiotherapy. They also
summarize their own original research on the prevalence of anemia in a typical
radiation oncology practice. Their study confirms that there is an
"epidemic" of anemia among oncology patients and suggests that the
issue requires far more attention than it has received.

A Prognostic Indicator

It is well recognized that anemia is associated with decreased response,
local control, and/or survival after radiotherapy, and the authors supply
numerous references to support this premise. Many of these studies addressed the
condition in the setting of radiotherapy alone, but is anemia still an important
prognostic factor now that concurrent chemoradiation has supplanted radiotherapy
alone for manyif not mostepithelial cancers? The Austrian experience cited
by Drs. Shasha and Harrison is thus very important in support of this
hypothesis.[1]

At the University of Pennsylvania Medical Center, we have observed a strong
relationship between hemoglobin level and response to preoperative
chemoradiation in patients with bulky stage IIIA non-small-cell lung
carcinoma.[2] We treated 41 patients (all with mediastinoscopy-proven bulky
stage IIIA disease) with neoadjuvant radiotherapy (45-50 Gy) and concurrent chemotherapy (either etoposide/cisplatin [Platinol] or
carboplatin [Paraplatin]/paclitaxel [Taxol]). Our results are listed in Table
1. Pathologic complete or near-complete (only tiny microscopic residual
foci) responses were seen in 12 of 23 patients with hemoglobin levels of 12.5 g/dL
or more vs 3 of 18 responses in patients with hemoglobin levels < 12.5 g/dL.
More studies are needed to determine the significance of anemia in the setting
of concurrent chemoradiation.

A Frequently Uncorrected Problem

In light of the strong evidence of a relationship between anemia and outcome,
why isn’t more emphasis placed on the correction of anemia? Drs. Shasha and
Harrison provide several possible reasons, including:

A lack of recognition of the problem;

The perception that the problem of anemia pales in comparison with other
treatment toxicities, such as infection and esophagitis;

The well-known infectious and immunologic risks of transfusion; and

The cost and logistical difficulties associated with the use of
recombinant human erythropoietin (epoetin alfa, Epogen, Procrit), including the
modest rate at which it increases hemoglobin.

Perhaps the most significant reason why the correction of anemia is still not
a standard intervention is the failure of the academic and clinical research
communities to prove that there is indeed a cause-and-effect relationship
between anemia and poor tumor control. In Figure 1 of their article, Drs. Shasha
and Harrison describe the traditional hypothesis that anemia leads to hypoxia,
which, in turn, leads to radioresistance and poor outcome. However, an
alternative explanation is that anemia/hypoxiawhich may be present for months
to years prior to cancer diagnosis and treatmentstimulates angiogenesis[3]
and, thus, tumor invasion and metastasis. In the angiogenesis model, correcting
anemia at this late stage in a cancer’s natural history may be ineffective.